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Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer

Abstract

CD40–CD40 ligand (CD40L) interaction is an important costimulatory signaling pathway in the crosstalk between T cells and antigen-presenting cells. This receptor–ligand system is known to be essential in eliciting strong cellular immunity. Here we demonstrate that murine lung cancer cells (3LLSA) transduced with the CD40L gene (3LLSA-CD40L) were rejected in syngeneic C57BL/6 mice, but grew in CD40-deficient mice to the same extent as control tumor cells. Immunohistochemical study showed that inflammatory cells, including CD4+, CD8+ T cells and NK cells, infiltrated into the inoculated 3LLSA-CD40L tumor tissue. Inoculation of 3LLSA-CD40L cells into mice resulted in the induction of 3LLSA-specific cytotoxic T-cell immunity, and the growth of parental 3LLSA tumors was inhibited when 3LLSA cells were inoculated into C57BL/6 mice mixed with 3LLSA-CD40L cells or when they were rechallenged 4 weeks after 3LLSA-CD40L cells were rejected. Furthermore, co-inoculation of interferon (IFN)-γ–transduced cells (3LLSA-IFNγ) with 3LLSA-CD40L cells enhanced the antitumor immunity efficiently in vivo. These results indicate that the in vivo priming with CD40L- and IFN-γ gene–transduced lung cancer cells is a promising strategy for inducing antitumor immunity in the treatment of lung cancer. Cancer Gene Therapy (2001) 8, 421–429

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Acknowledgements

The authors thank Keiko Shimamoto for her continuous technical assistance throughout our work. This work was supported by a grant-in-aid for COE Research from the Ministry of Education, Science, Sports and Culture of Japan and the 25th Aichi Cancer Research Foundation.

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Correspondence to Yoshinori Hasegawa.

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Noguchi, M., Imaizumi, K., Kawabe, T. et al. Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer. Cancer Gene Ther 8, 421–429 (2001). https://doi.org/10.1038/sj.cgt.7700320

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